title: A phase 1 trial of PfCP2.9: an AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria.
abstract: Apical Membrane Antigen 1 (AMA1) and Merozoite Surface Protein 1 (MSP1) were produced as a recombinant fusion protein and formulated with the adjuvant Montanide ISA 720 with the aim of replicating the structure present in the parasite protein. A previous trial with this construct demonstrated the vaccine was safe and immunogenic but was associated with injection site reactogenicity. This Phase 1a dose-escalating, double blind, randomized, controlled trial of PfCP2.9/Montanide ISA 720 was conducted to evaluate alternative dose levels and vaccination schedules, with a pre-formulated vaccine that had undergone more in-depth and frequent quality control and stability analysis. The trial was conducted in seventy healthy Chinese malaria-naïve volunteers between January 2006 and January 2007. The objective was to assess the safety, reactogenicity and immunogenicity of 5, 20 and 50microg of PfCP2.9/ISA 720 under 2 different schedules. The most common adverse event was injection site tenderness (53%). The frequency and severity of adverse events was similar in both vaccination schedules. Antibody responses were induced and remained elevated throughout the study in volunteers receiving vaccine (p<0.001). Although high antibody titers as measured by ELISA to the PfCP2.9 immunogen were observed, biological function of these antibodies was not reflected by the in vitro inhibition of parasite growth, and there was limited recognition of fixed parasites in an immunofluorescence assay. At all three dose levels and both schedules, this formulation of PfCP2.9/ISA 720 is well tolerated, safe and immunogenic; however no functional activity against the parasite was observed.
authors.affiliation: PATH Malaria Vaccine Initiative, Bethesda, MD, USA. malkine@medimmune.com
authors.forename: Elissa
authors.initials: E
authors.lastname: Malkin
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.forename: Xinling
authors.initials: X
authors.lastname: Bi
authors.forename: Zarifah
authors.initials: Z
authors.lastname: Reed
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Xuegong
authors.initials: X
authors.lastname: Pan
authors.forename: Tom
authors.initials: T
authors.lastname: Chen
authors.forename: Birgitte
authors.initials: B
authors.lastname: Giersing
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Kang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tucker
authors.forename: Eveline
authors.initials: E
authors.lastname: Tierney
authors.forename: Weiqing
authors.initials: W
authors.lastname: Pan
authors.forename: Carole
authors.initials: C
authors.lastname: Long
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000032:analysis / Q000096:biosynthesis; D002135:Calcium-Binding Proteins / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D017780:Malaria Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D050506:Mutant Chimeric Proteins / Q000276:immunology; D010843:Pichia / Q000737:chemistry / Q000276:immunology; D011494:Protein Kinases / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D018401:Sample Size; D014614:Vaccines, Synthetic / Q000276:immunology*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D002135:Calcium-Binding Proteins; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D050506:Mutant Chimeric Proteins; C535092:PfCP2.9 vaccine; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; D011494:Protein Kinases; C079866:PfCPK protein, Plasmodium falciparum